The halogen-mediated opening of epoxides in the presence of pyridine-containing macrocycles

Article abstract of DOI:10.1016/S0040-4020(01)00443-4

The ring opening of epoxides with elemental iodine and bromine in the presence of three pyridine-containing macrocyclic diamides as new catalysts affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs regioselectively under mild conditions in various aprotic solvents. The catalysts are easily recovered and can be reused several times.

Full text of DOI:10.1016/S0040-4020(01)00443-4

TETRAHEDRON
Pergamon
Tetrahedron 57 =2001) 6057±6064
The halogen-mediated opening of epoxides in the presence of
pyridine-containing macrocycles
Hashem Sharghi,a,p Khodabakhsh Niknamb and Maryam Pooyana
aDepartment of Chemistry, College of Science, Shiraz University, Shiraz 71454, Iran
bDepartment of Chemistry, College of Science, Persian Gulf University, Bushehr 75168, Iran
Received 18 October 2000; revised 2 April 2001; accepted 20 April 2001
AbstractÐThe ring opening of epoxides with elemental iodine and bromine in the presence of three pyridine-containing macrocyclic
diamides as new catalysts affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs regioselectively under
mild conditions in various aprotic solvents. The catalysts are easily recovered and can be reused several times. q 2001 Elsevier Science Ltd.
All rights reserved.
1. Introduction
epoxides. Three pyridine-containing macrocyclic dilactams
were selected as catalysts in these reactions.
Vicinal halo alcohols have attained great signi®cance in
organic synthesis.1±3 These compounds can be utilized for
some useful synthetic transformations,4,5 and are also key
intermediates in the synthesis of halogenated marine natural
products.1 Avariety of reagents such as hydrogen halides or
hydrohalogenic acids,6 are known to convert epoxides to
halohydrins. However, these procedures suffer from certain
limitations when protic acid-sensitive substrates are used.
The ring opening of unsymmetrically substituted epoxides
with Li2[NiBr4],7 pyridine´HCl,8 haloboran reagents,9±12
Br2/PPh3,13 Ti=O±iPr)4,14 chlorosilanes,15 [n-Bu4N]Br/
Mg=NO3)2,16 Lewis acid metal halides,2,3,17,18 and Me3SiBr19
have been reported. However, these methods are not always
fully satisfactory, and suffer from disadvantages, such as
acidity, handling and in situ preparation of the reagent, the
noncatalytic nature of the reagents and relatively long reac-
tion times.11,15,20±22 Recently, it has been found that
epoxides can be converted into iodohydrins and bromo-
hydrins by means of elemental iodine and bromine,23 but
this method has some limitations such as low yield and
regioselectivity with long reaction times and formation of
acetonide byproducts in addition to the expected iodoadduct
in acetone solution. Furthermore, iodination does not occur
in CH2Cl2, CHCl3, C6H6, CH3CN, and THF solvents.
2. Result and discussion
In recent years, there has been considerable interest in the
use of macrocyclic ionophores incorporating heterocyclic
subunits, because of their ability to form strong and selec-
tive interactions with various charged and neutral guest
molecules. Pyridine and other nitrogen-containing hetero-
cyclic groups incorporated in the macrocyclic ring provide
rigidity and are able to participate in complexation through
their soft nitrogen donor atoms. Pyridine-containing macro-
cycles are ef®cient complexing agents for metal cations.27
They also displayed high log K values in complexation with
ammonium salts.27±29 Because of these interesting complex-
ing properties, it is important to have a high yield for synth-
eses of these macrocyclic diamides.
In previous studies,24 we reported a new ef®cient synthesis
of macrocyclic diamides. No high-dilution technique was
required in this method. We applied this approach to the
synthesis of dilactams 1a±c =Scheme 1).
o-Nitrophenol was reacted with dichlorides of olygoethyl-
ene glycols in the presence of potassium carbonate in
dimethylformamide to yield the corresponding dinitro
compounds 4a±c in the range of 67±85% yields. The dinitro
compounds 4a±c were reduced by palladium on carbon with
hydrazine into corresponding diamines 5a±c in 94, 93 and
83% yields respectively.
In conjunction with the ongoing work in our laboratory on
the synthesis and complex formation of macrocyclic
compounds with neutral molecules such as iodine and
bromine,24±26 we found that these compounds ef®ciently
catalyzed the addition of elemental iodine and bromine to
The cyclization reaction between 2,6-pyridine dicarboxylic
acid dichloride and the diamines 5a±c was performed with-
out the use of high-dilution techniques. In addition, the
Keywords: macrocyclic diamides; halo alcohols; epoxides.
Corresponding author. Tel.: 198-711-2227601-3; fax: 198-711-2220027
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020=01)00443-4

6058
H. Sharghi et al. / Tetrahedron 57 *2001) 6057±6064
Scheme 1.
cyclization reaction was carried out with fast addition of a
solution of diamine =2 mmol) in dry CH2Cl2 =10 ml) into a
solution of 2,6-pyridine dicarboxylic acid dichloride
=2 mmol) in dry CH2Cl2 =10 ml) over 5 s with vigorously
stirring at room temperature. The reaction mixture was
stirred for further 20 min to give pyridine-containing macro-
cyclic diamides 1a±c in the range of 78±82% yields
=Scheme 1).
elemental iodine in the absence of catalyst did not occur
even under re¯ux and extension of reaction time to several
days, and unreacted styrene oxide was completely recov-
ered. In addition, the yield of the bromination reactions is
very low in the absence of catalyst.
The results obtained with some representative epoxides in
the presence of macrocycle 1c as catalyst are summarized in
Table 2 and are compared with the corresponding results
obtained in the reaction of the same epoxides in the absence
of catalyst =Table 2, entries 2, 4, 6, 9 and 12). When
epoxides were allowed to react in the presence of a catalyst,
an increase in the yields and regioselectivies were observed
in all of the reactions studied. Generally, the optimum
amounts of the catalyst were found to be 0.1 mol for
1 mol of epoxide and halogen.
Epoxides of convenient volatility to allow GC analysis were
chosen for study. As catalysts, three pyridine-containing
macrocyclic diamides that were synthesized according to
Scheme 1 were used. The result of the reactions of styrene
oxide with elemental iodine and bromine in the presence of
the above catalysts are summarized in Table 1. In each case,
cleavage of epoxide ring occurs and upon thiosulfate
workup, the corresponding iodohydrin and bromohydrin
were obtained. The catalysts were easily recovered and
could be reused several times. In comparison, the cleavage
behavior of styrene oxide with elemental iodine and
bromine in the absence of catalyst is given in entries 1,2
and 7.
However, the following factors can in¯uence the yield and
regioselectivity of the reactions: =1) the steric hindrance of
epoxides, =2) the rate of admixing the reagents, =3) the order
in which the reagents are combined, and =4) the nature of
solvent. In cases of the rate and order in which the reagents
are combined, for example, if bromine before the catalyst is
added to epoxide, two isomeric bromo alcohols are
produced. However, if the epoxide is added to the catalyst,
and then bromine is added dropwise over a period of time,
only one isomer is formed. Furthermore, the rapid addition
of bromine reduced the regioselectivity.
As shown in Table 1, yields for both iodination and bromi-
nation with this methodology are quite good. Catalyst 1c is
the most effective, and reactions occur instantaneously in
the presence of this catalyst =Table 1, entries 6 and 11).
However, iodination of styrene oxide with an excess of

H. Sharghi et al. / Tetrahedron 57 *2001) 6057±6064
6059
Table 1. Reaction of styrene oxide with elemental iodine and bromine in the presence of representative catalysts
Entry
Catalyst
Conditions
Time =h)
Yielda =%)
Product=s)
Ref.
23
1
2
3
±
±
±
I2, rt, acetone
2
±
83
I2 =excess)/CH2Cl2
LiI, AcOH, THF, rt
±
N.R.
23
1.3
87 =1:2)
22
4
1a
I2, rt/CH2Cl2
0.33
0.33
immed.
1
80
50
5
1b
I2, rt/CH2Cl2
6
1c
I2, rt/CH2Cl2
.95
60
7
18-Crown-6
KI3, rt H2O/CH2Cl2
Br2, rt/CH2Cl2
Br2, rt/CH2Cl2
Br2, rt/CH2Cl2
Br2, rt/CH2Cl2
8
±
1
31
23
9
1a
1b
1c
0.16
0.16
immed.
93
10
11
92
.95
12
13
14
±
±
±
n-Bu4N1Br2/ Mg=NO3)2,
CHCl3
5
78 =5:1)
75 =1:4.5)
.99
7
11
20
=Me2N)2BBr/CH2Cl2, N2 atm.
HBr, CHCl3
12
0.25
15
±
HI, CHCl3
0.25
.99
20
a
GC yield.
The results of a halogenative cleavage of styrene oxide with
iodine and bromine by catalyst 1c in various aprotic solvents
are reported in Table 3. The iodination and bromination
reactions proceed most cleanly in CH2Cl2, CHCl3,
CH3CN, and benzene solution, while those done in THF
and acetone lead to a lower yield of halohydrins.
tivity is generally observed in these reactions. In many
cases, this type of regioselectivity appears to be the opposite
of that observed in ring opening of the same epoxides with
aqueous hydrogen halides under classic acidic conditions
=entries 14 and 15, Table 1).
The regiochemical mode of epoxide cleavage by elemental
iodine or bromine in the presence of macrocycle catalyst can
be viewed as occurring via nucleophilic attack by the halide
ion on the less sterically hindered epoxide carbon. This
mechanism closely resembles the SN2 model for aliphatic
nucleophilic displacement. On the basis of our previous
As shown in Table 2 =entries 10 and 11), in which only the
trans isomer is obtained, the reactions are completely anti-
stereoselective. As for the regioselectivity, an attack of the
nucleophile preferentially occurs at the less-substituted
oxirane carbon. An anti-Markovnikov-type30 regioselec-

6060
H. Sharghi et al. / Tetrahedron 57 *2001) 6057±6064
Table 2. Reaction of epoxides with elemental iodin and bromine in the presence of representative catalysts
Entry
1
Epoxide
Catalyst
Conditions
Time =h)
5
Yielda =%)
Product=s)
Ref.
1c
I2, rt, CH2Cl2
.95
2
±
I2, rt, acetone
±
94 =1:1)
23
3
4
1c
Br2, rt CH2Cl2
Br2, rt CH2Cl2
0.3
.95
±
±
88 =5:1)
23
5
6
1c
±
I2, rt, CH2Cl2
16
±
89
I2, acetone
79 =1:4)
23
7
1c
1c
1c
1c
Br2, rt CH2Cl2
I2, rt, CH2Cl2
Br2, rt CH2Cl2
I2, rt, CH2Cl2
0.33
88
80
87
86
8
4
9
0.75
6
10
11
1c
Br2, rt, CH2Cl2
0.33
5
88
90
12
13
±
LiBr, AcOH, THF, rt
22
1c
1c
I2, rt, CH2Cl2
18
78
85
14
Br2, rt, CH2Cl2
0.33
a
GC yield.
study on macrocycle diamides23±26 and other works on the
complexation of crown ethers with elemental halogens,
halogenative cleavage of epoxides occurs according to the
following four-step mechanism:
halogen, in which halogen ion =X32) exists as a contact
ion pair:
Macrocycle 1 2X2 ! ꢀmacrocycle¼X1†X32
or
The ®rst step involves the formation of a 1:2 or 1:1
molecular complex between macrocycle and elemental
2 Macrocycle 1 2X2 ! ꢀ2 macrocycle¼X1†X2
ꢀ1†

H. Sharghi et al. / Tetrahedron 57 *2001) 6057±6064
6061
Table 3. Halogenation reaction of styrene oxide in the presence of 0.1 mol
of catalyst 1c in various solvents
on the epoxide or epoxide±halogen complex, giving the
more stable transition state =B):
Time =h)
Bromination Iodination Bromination Iodination
Yielda =%)
Entry
Solvent
CH2Cl2
CHCl3
C6H6
CH3CN
CH3COCH3
THF
1
2
3
4
5
6
0.3
0.5
0.6
0.6
2
0.03
0.3
0.5
1
10
10
.95
.95
.95
90
85
65
.95
.90
92
90
75
2
30
a
GC yield.
In the second step this complex is further decomposed to
release X3 ion into solution as
2
Most Lewis acidic compounds, such as titanium halides,
foster electrophilic opening of the epoxide ring to yield
transition state A. When weaker Lewis acids are employed,
namely bromine or iodine, nucleophilic attack, by the halide
ions generated should be fostered and transition state B may
be expected to be lower in energy. In this case, the cleavage
leads to a mixture of secondary alcohol and primary alcohol
products.3
ꢀMacrocycle¼X13 †X2 ! ꢀmacrocycle¼X1† 1 X23
Therefore, in this way, molecular iodine or bromine is
converted to a nucleophilic halogen species in the presence
of a suitable macrocycle and, in the third step, this ion
participates in the ring opening reaction of epoxides
ꢀ2†
ꢀ3†
The variation in yield and rate of cleaving epoxides by
elemental iodine or bromine in the presence of these cata-
lysts =1a±c) can be satisfactorily rationalized in terms of the
suggested mechanism. The macrocycle 1c is the most active
catalyst in these reactions.
Finally, the catalyst is regenerated in step 4.
ꢀ4†
These steps occur continuously until all of the epoxides and
halogen are consumed, and after workup, the catalyst can be
recovered easily.
In support of this mechanism, reaction of catalysts with
iodine was followed by UV spectroscopy =Fig. 1). Fig. 1
shows a characteristic band in 364 nm is well known to be
2 31±34
speci®c for the formation of triiodide ion, I3
.
On the other hand, when catalyst is not present, cleavage of
epoxides can occur via two limiting mechanistic pathways,
either electrophilic attack by molecular halogen, behaving
as Lewis acid, giving the more stable carbonium ion-like
transition state =A), or via nucleophilic attack by halide ion
The decrease in regioselectivity that results by merely rever-
sing the order of mixing of epoxide and halogen, namely the
slow addition of bromine to epoxide, before catalyst was
added, can readily be understood from the model. When
Figure 1. Absorption spectra of used macrocycle±iodine complexes. Spectra from bottom to top refer to iodine and macrocycles 1a, 1b and 1c: iodine
complexes.

6062
H. Sharghi et al. / Tetrahedron 57 *2001) 6057±6064
the initial epoxide was introduced =in the absence or
presence of catalyst), it would encounter an excess amount
of bromine; electrophilic attack by bromine can then occur,
giving the transition state A, and bromine anions will attack
the more substituted carbon. On the other hand, slow
addition of bromine to the mixture of catalyst and epoxide
fosters the four-step mechanism presented above in which
all of the elemental bromine is converted to Br3 by the
catalyst and it then attacks the less substituted carbon
selectivity.
NMR =CDCl3, 250 MHz) d 3.58 =s, 4H), 3.88 =t, 4H, Jˆ
4.65 Hz), 4.12 =t, 4H, Jˆ4.65 Hz), 6.59±6.78 =m, 8H).
3.1.2. 1,8-Bis 'o-aminophenoxy)-3,6-dioxaoctane '5b).35
White crystals, yield 93%, mpˆ48±508C; IR =KBr): 750
=m), 950 =m), 1060 =m), 1140 =m), 1225 =s), 1275 =s),
1510 =m), 1608 =m), 2885 =m), 2940 =m), 3060 =s), 3370
2
1
=s), 3470 =s) cm21; H NMR =CDCl3, 250 MHz) d 3.67 =s,
4H), 3.77 =s, 4H), 3.85 =t, 4H, Jˆ4.5 Hz), 4.2 =t, 4H, Jˆ
4.5 Hz), 6.54±6.77 =m, 8H); Mass m/z =%): 333=M111,
7.0), 332=M1, 32.7), 224=17.7), 153=12), 136=49.2),
109=57.1), 92=38.3), 80=53.1), 65=30.9), 44=base peak).
In conclusion, we have found that suitable pyridine-contain-
ing macrocyclic compounds can catalyze the regioselective
ring opening of epoxides by elemental iodine and bromine
under neutral conditions with a variety of sensitive func-
tional groups, as well as the convenience of this procedure,
which make this synthetic technique highly useful.
3.1.3. 1,5-Bis 'o-aminophenoxy)-3-thiopentane '5c).
White crystals, yield 89%, mpˆ28±298C; IR =KBr): 735
=m), 1017 =m), 1212 =s), 1273 =m), 1470 =m), 1508 =s),
1608 =m), 2871 =w), 2928 =w), 3070 =w), 3328 =m), 3408
1
=s) cm21; H NMR =CDCl3, 250 MHz) d 3.03 =t, 4H, Jˆ
6.50 Hz), 3.73 =b, 4H), 4.20 =t, 4H, Jˆ6.50 Hz), 6.66±
6.84 =m, 8H); Mass m/z =%): 304=M1, 2.5), 196=12.6),
168=23.4), 123=18.8), 105=base peak), 80=32.4), 61=53.8),
45=65.6).
3. Experimental
IR spectra were obtained on an Impact 400 D Nickolet FTIR
spectrophotometer. NMR spectra were recorded on a
Brucker Avance DPX-250 =90 MHz) in pure deuterated
solvents. UV±vis spectra were obtained with a Philips
PU8750 spectrometer. Mass spectra were determined on a
Shimadzu GCMS-QP 1000 EX instrument at 70 ev. The
purity determination of the substrates and reactions
monitoring were accomplished by TLC on silica gel poly-
gram SILG/UV 254 plates or GLC on a Shimadzu GC-10A
instrument with a ¯ame ionization detector using a column
of 15% carbowax 20 M chromosorb W acid washed 60±80
mesh. Elemental analyses were performed at the National
Oil Co. of Iran at Tehran Research Center. Column
chromatography was carried out on short columns of silica
gel 60 =230±400 mesh) in glass columns =2±3 cm diameter)
using 15±30 g of silica gel per 1 g of crude mixture. Melting
points were determined in open capillary tubes in a buchi-
510 circulating oil melting point apparatus. Epoxides, and
other chemical materials were purchased from Fluka
and Merck in high purity and were used without further
puri®cation.
3.1.4.
3,15,21-Triaza-4,5;13,14-dibenzo-6,9,12-trioxa-
bicyclo[15.3.1]heneicosa-1'21),17,19-triene-2,16-dione
'1a). White crystals; yield 82%; mp 223±2248C; IR =KBr):
3395.52 =NH), 1682.84 cm21 =CO); 1H NMR =CDCl3,
250 MHz), d 3.86 =t, 4H, Jˆ4.0 Hz), 4.20 =t, 4H, Jˆ
4.0 Hz), 6.80 =dd, 2H, J1ˆ7.85 Hz, J2ˆ1.75 Hz), 6.94 =dt,
2H, J1ˆ7.75 Hz, J2ˆ1.75 Hz), 7.08 =dt, 2H, J1ˆ7.75 Hz,
J2ˆ1.8 Hz), 8.00 =t, 1H, Jˆ6.35 Hz), 8.18 =dd, 2H, J1ˆ
7.75 Hz, J2ˆ1.8 Hz), 8.47 =dd, 2H, J1ˆ7.8 Hz, J2ˆ
1.65 Hz), 9.64 =s, 2H); UV =chloroform) l =1max): 248
=10741), 300.3 nm =12489); MS m/z 421 =M112, 5.5),
420 =M111, 29.8), 419 =M1, base peak), 375 =12.3), 331
=4.1), 214 =22.4), 134 =77.9), 107 =18.2); Anal. Calcd for
C23H21N3O5: C, 65.86; H, 5.05; N, 10.02. Found: C, 65.73;
H, 5.13; N, 9.92.
3.1.5. 3,18,24-Triaza-4,5;16,7-dibenzo-6,9,12,15-tetra-
oxabicyclo[18.3.1]tetra-eicosa-1'24),20,22-triene-2,19-
dione '1b). White crystals; yield 78%; mp 139±1418C; IR
=KBr):3314.93 =NH), 1682.84 cm21 =CO); 1H NMR
=CDCl3, 250 MHz), d 3.51 =s, 4H), 3.74 =t, 4H, Jˆ
4.0 Hz), 4.20 =t, 4H, Jˆ4.0 Hz), 7.00±7.16 =complex, 6H),
8.01 =t, 1H, Jˆ8.3 Hz), 8.10 =d, 2H, Jˆ7.8 Hz), 8.43 =d, 2H,
Jˆ6.3 Hz), 10.12 =b, 2H); UV =chloroform) l =1max): 243.7
=9250), 302.7 nm =9991); MS m/z 465 =M112, 7.0), 464
=M111, 28.9), 463 =M1, 24.1), 409 =16.2), 248 =12.9),
214 =29.1), 134 =99.3), 106 =41.6), 92 =16.0), 45 =base
peak); Anal. Calcd for C25H25N3O6: C, 64.79; H, 5.44; N,
9.06. Found: C, 64.91; H, 5.59; N, 8.81.
3.1. General procedure for the preparation of diamino
compounds 5a±c
In a two necked round-bottomed ¯ask =250 ml) equipped
with a re¯ux condenser and a dropping funnel, a suspension
of dinitro compounds 4a±c =0.012 mol), palladium on
carbon 5% =0.4 g) and absolute ethanol =200 ml) was
prepared. The mixture was warmed and while being stirred
magnetically, hydrazine hydrate 80% =10 ml) in ethanol
=20 ml) was added dropwise over a 1.5 h period through
the dropping funnel, while maintaining the temperature at
about 508C. The reaction mixture was re¯uxed for 2 h and
®ltered while hot. On cooling the ®ltrate gave the corre-
sponding diamino compound after vacuum dried.
3.1.6. 3,15,21-Triaza-4,5;13,14-dibenzo-6,12-dioxa-9-thia-
bicyclo[15.3.1]heneicosa-1'21),17,19-triene-2,16-dione
'1c). White cream crystals; yield 80%; mp 168±1708C; IR
=KBr): 3382.22 =NH), 1682.84 cm21 =CO); 1H NMR
=CDCl3, 250 MHz), d 3.02 =t, 4H, Jˆ5.4 Hz), 4.38 =t, 4H,
Jˆ5.4 Hz), 7.00 =dd, 2H, J1ˆ7.45 Hz, J2ˆ1.8 Hz), 7.05±
7.17 =m, 4H), 8.13 =t, 1H, Jˆ7.8 Hz), 8.43 =dd, 2H, J1ˆ
7.55 Hz, J2ˆ2.1 Hz), 8.45 =d, 2H, Jˆ7.8 Hz), 10.00 =s,
2H); UV =chloroform) l =1max): 244.5 =11294.5), 304 nm
=12832.5); MS m/z 437 =M112, 5.8), 436 =M111, 20.6),
3.1.1. 1,5-Bis 'o-aminophenoxy)-3-oxapentane '5a).
White crystals, yield 94%, mpˆ65±668C =lit.24: 63±
658C); IR =KBr): 735 =s), 950 =m), 1050 =m), 1138 =m),
1212 =s), 1273 =m), 1460 =m), 1508 =s), 1595 =m), 1605
=m), 2880 =w), 2932 =m), 3321 =s), 3388 =s) cm21 1H
;

H. Sharghi et al. / Tetrahedron 57 *2001) 6057±6064
6063
435 =M1, 24.6), 375 =2.6), 331 =2.8), 214 =5.7), 187 =9.2),
134 =15.3), 120 =7.3), 105 =13.4), 93 =3.3), 87 =base peak);
Anal. Calcd for C23H21N3O4S: C, 63.43; H, 4.86; N, 9.65; S,
7.36. Found: C, 63.69; H, 4.59; N, 9.91; S, 7.09.
62.89 MHz) d 22.3, 35.4, 69.6, 70.4, 72.7; IR =neat) 675
=m), 798 =w), 923 =m), 1051 =s), 1085 =s), 1125 =m), 1375
=m), 1467 =m), 2871 =m), 2925 =m), 2972 =s), 3435 =br
s) cm21
.
3.2.6. 1-'Isopropyloxy)-3-iodo-2-propanol. 1H NMR
=CDCl3, 250 MHz) d 1.15 =d, 6H, Jˆ4.0 Hz), 2.92 =s,
1H), 3.38±3.59 =m, 5H), 3.79 =m, 1H); 13C NMR =CDCl3,
62.89 MHz) d 22.8, 36.2, 67.3, 69.8, 72.5; IR =neat) 743
=w), 923 =m), 1050 =s), 1085 =s), 1128 =s), 1375 =m), 1467
3.2. General procedure for halogenative cleavage of
epoxides
Epoxide =1 mmol) in CH2Cl2 =5 ml) was added to a stirred
solution of catalyst =0.1 mmol) in CH2Cl2 =5 ml) at room
temperature. Next, a solution of elemental halogen
=1 mmol) in CH2Cl2 =5 ml) was added portionwise
=15 min) to the above mixture. The progress of the reaction
was monitored by GLC and TLC. After complete disappear-
ance of the starting material, the reaction mixture was
washed with 10% aqueous Na2S2O3 =2£10 ml) and water
=2£10 ml). The aqueous layer was extracted with CH2Cl2
=2£10 ml).The combined organic layer was dried over
anhydrous MgSO4 and evaporated to give crude alcohol±
catalyst. The crude products were puri®ed by crystallization
in diethyl ether. After cooling, the catalyst was ®ltered off
and washed with cold ether. The solvent was evaporated and
pure halohydrin was obtained. The halohydrins obtained
throughout this procedure were identi®ed by comparison,
where possible, with authentic samples prepared in accor-
dance with literature procedures.18,22,23,36,37
=m), 2870 =m), 2926 =m), 2975 =s), 3472 =br s) cm21
.
1
3.2.7. 1-Phenoxy-3-bromo-2-propanol. H NMR =CDCl3,
250 MHz) d 2.75 =s, 1H), 3.61 =d, 2H, Jˆ5.0 Hz), 4.03 =m,
1H), 4.11 =d, 2H, Jˆ7.0 Hz), 6.78 =d, 1H, Jˆ5.0 Hz), 6.94
=d, 2H, Jˆ8.0 Hz), 7.35 =m, 2H); 13C NMR =CDCl3,
62.89 MHz) d 69.6, 69.8, 69.9, 115.0, 116.8, 121.9, 130.0,
132.8; IR =neat) 641 =w), 688 =m), 756 =m), 823 =m), 1038
=s), 1112 =w), 1239 =s), 1375 =m), 1494 =s), 1588 =s), 2878
=m), 2925 =s), 3059 =m), 3415 =br s) cm21
.
3.2.8. 1-Phenoxy-3-iodo-2-propanol. 1H NMR =CDCl3,
250 MHz) d 3.10 =s, 1H), 3.48 =d, 2H, Jˆ5.0 Hz), 4.06
=m, 1H), 4.13 =d, 2H, Jˆ5.6 Hz), 6.78±6.90 =m, 3H), 7.36
=m, 2H); 13C NMR =CDCl3, 62.89 MHz) d 67.2, 69.7, 70.0,
115.0, 116.9, 121.8, 129.9, 132.9; IR =neat) 650 =w), 678
=w), 760 =m), 823 =m), 1038 =s), 1113 =w), 1240 =s), 1375
=m), 1494 =s), 1588 =s), 2877 =m), 2927 =s), 3050 =m), 3418
1
3.2.1. 1-Bromo-2-octanol. H NMR=CDCl3, 250 MHz) d
=br s) cm21
.
0.89 =t, 3H, Jˆ6.5 Hz), 1.25±1.63 =m, 8H), 1.86 =q, 2H,
Jˆ7.1 Hz), 2.22 =s, 1H), 3.42 =t, 2H, Jˆ7.1 Hz), 3.75±
3.84 =m, 1H); 13C NMR =CDCl3, 62.89 MHz) d 14.0,
22.5, 25.6, 29.1, 31.7, 35.05, 40.7, 71.0; IR =neat) 720
=m), 830 =m), 1050 =s), 1075 =s), 1125 =m), 1225 =m),
1265 =m), 1385 =m), 1425 =m), 1470 =s), 2860 =vs), 2935
3.2.9. 1-'p-Tolyloxy)-3-bromo-2-propanol. 1H NMR
=CDCl3, 250 MHz) d 2.12 =s, 1H), 2.53 =s, 3H), 3.16 =d,
2H, Jˆ5.0 Hz), 3.47 =m, 1H), 4.11 =d, 2H, Jˆ7.0 Hz),
6.93 =d, 2H, Jˆ8.8 Hz), 7.19 =d, 2H, Jˆ7.5 Hz); 13C NMR
=CDCl3, 62.89 MHz) d 26.2, 59.8, 69.4, 70.65, 95.9, 115.3,
130.4, 157.2; IR =neat) 659 =s), 819 =m), 1016 =s), 1075 =w),
1123 =s), 1242 =s), 1285 =m), 1381 =w), 1458 =m), 1512 =s),
1585 =m), 1613 =m), 2875 =m), 2927 =s), 2962 =m), 3035
=vs), 2970 =vs), 3380 =br s) cm21
.
1
3.2.2. 1-Iodo-2-octanol. H NMR =CDCl3, 250 MHz) d
0.89 =t, 3H, Jˆ7.0 Hz), 1.26±1.58 =m, 10H), 2.24 =s, 1H),
3.24±3.55 =m, 3H); 13C NMR =CDCl3, 62.89 MHz) d 14.1,
16.45, 22.6, 25.6, 29.1, 31.7, 36.9, 70.9; IR =neat) 725 =m),
1015 =br s), 1105 =m), 1130 =m), 1185 =s), 1385 =s), 1425
=m), 1470 =s), 2860 =vs), 2935 =vs), 2970 =vs), 3380 =br
=m), 3425 =br, s) cm21
.
3.2.10. 1-'p-Tolyloxy)-3-iodo-2-propanol. 1H NMR
=CDCl3, 250 MHz) d 2.15 =s, 1H), 2.49 =s, 3H), 3.02 =d,
2H, Jˆ4.1 Hz), 3.46 =m, 1H), 4.16 =d, 2H, Jˆ5.6 Hz),
6.95 =d, 2H, Jˆ8.5 Hz), 7.23 =d, 2H, Jˆ8.2 Hz); 13C NMR
=CDCl3, 62.89 MHz) d 24.1, 58.3, 66.2, 69.4, 95.8, 114.45,
130.1, 156.8; IR =neat) 665 =s), 743 =w), 814 =m), 1015 =s),
1072 =w), 1123 =s), 1240 =s), 1286 =m), 1378 =w), 1462 =m),
1512 =s), 1586 =m), 1611 =m), 2875 =m), 2928 =s), 2962 =m),
s) cm21
.
3.2.3. 2-Bromocyclohexanol. 1H NMR =CDCl3, 250 MHz)
d 1.26±1.42 =m, 3H), 1.78±1.98 =m, 3H), 2.18±2.32 =m,
1H), 2.32±2.38 =m, 1H), 2.68 =s, 1H), 3.58±3.64 =m, 1H),
3.82±3.92 =m, 1H); 13C NMR =CDCl3, 62.89 MHz) d 24.5,
27.0, 33.95, 36.6, 62.1, 75.7; IR =neat) 690 =s), 793 =w), 865
=m), 960 =s), 1038 =m), 1075 =br s), 1123 =m), 1189 =s), 1372
3038 =m), 3422 =br, s) cm21
.
3.2.11. 2-Bromo-1-phenylethanol. 1H NMR =CDCl3,
250 MHz) d 1.98 =s, 1H), 4.01 =m, 2H), 4.98 =t, 1H, Jˆ
5.0 Hz), 7.19±7.39 =m, 5H); 13C NMR =CDCl3,
62.89 MHz) d 57.4, 68.0, 128.3, 129.3, 129.4, 139.0; IR
=neat) 689 =m), 766 =m), 823 =m), 1036 =s), 1115 =w),
1233 =s), 1375 =m), 1494 =m), 1600 =s), 2875 =m), 2935
=m), 1460 =s), 2882 =s), 2960 =br s), 3425 =br s) cm21
.
1
3.2.4. 2-Iodocyclohexanol. H NMR =CDCl3, 250 MHz) d
1.26±1.44 =m, 3H), 1.75±1.95 =m, 3H), 2.15±2.30 =m, 1H),
2.30±2.35 =m, 1H), 2.72 =s, 1H), 3.58±3.62 =m, 1H), 3.90±
4.00 =m, 1H); 13C NMR =CDCl3, 62.89 MHz) d 24.5, 26.6,
32.75, 35.4, 59.8, 71.6; IR =neat) 690 =s), 790 =w), 870 =m),
948 =s), 1038 =w), 1082 =br s), 1123 =m), 1189 =s), 1372 =m),
=s), 3064 =m), 3405 =br, s) cm21
.
3.2.12. 2-Iodo-1-phenylethanol. 1H NMR =CDCl3,
250 MHz) d 2.02 =s, 1H), 3.76 =d, 2H), 4.78 =t, 1H, Jˆ
5.0 Hz), 7.17±7.35 =m, 5H); 13C NMR =CDCl3,
62.89 MHz) d 54.7, 66.9, 128.2, 129.1, 129.2, 138.2; IR
=neat) 748 =m), 915 =m), 1032 =s), 1121 =w), 1243 =s),
1462 =s), 2882 =s), 2960 =br s), 3425 =br s) cm21
.
3.2.5. 1-'Isopropyloxy)-3-bromo-2-propanol. 1H NMR
=CDCl3, 250 MHz) d 1.16 =d, 6H, Jˆ4.0 Hz), 2.78 =s,
1H), 3.42±3.65 =m, 5H), 3.92 =m, 1H); 13C NMR =CDCl3,

6064
H. Sharghi et al. / Tetrahedron 57 *2001) 6057±6064
16. Suh, Y. G.; Koo, B. A.; Ko, J. A.; Cho, Y. S. Chem. Lett. 1993,
1907.
1365 =m), 1492 =m), 1602 =s), 2885 =m), 2930 =s), 3061 =m),
3398 =br, s) cm21
.
17. Bonini, C.; Righi, G.; Sotgiu, G. J. Org. Chem. 1991, 56, 6206.
18. Iranpoor, N.; Kazemi, F.; Salehi, P. Synth. Commun. 1997, 27,
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Acknowledgements
19. Kricheldorf, H. R.; Morber, G.; Regel, W. Synthesis 1981,
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We gratefully acknowledge the support of this work by the
Shiraz University Research Council.
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1992, 48, 3805.
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